Sugar-based synthesis of an enantiomorphically pure zeolite

Zeolites, well-known by their high selectivities in catalytic and separation processes due to their porous nature, play a crucial role in various applications. One significant long-term objective is the synthesis of enantiopure zeolites, potentially enabling enantioselective processes. Earlier attempts result in partial success, yielding some enantiomorphically enriched zeolites. In this study, we introduce a zeolite synthesis approach utilizing chiral organic structure directing agents (ch-OSDAs) derived from sugars, guiding the crystallization process toward achieving enantiomorphically pure S-STW zeolite. The purity of the zeolite is confirmed through extensive analyses of individual crystals using single-crystal X-ray diffraction, extracting Flack parameters and space groups. Theoretical and structural investigations confirm that the sugar-derived ch-OSDA perfectly fits the characteristic helicoidal channel of the zeolite structure, featuring its efficacy in achieving enantiopure zeolites.

The work described in this manuscript is very good.The topic of chiral molecular sieves is appropriate for Nature Communications, and the results of sufficient significance to merit publication.I have a few comment to hopefully assist in constructing the final version of the manuscript.
1.There is really no way to prove that a powder is enantiomerically pure.The authors have done a good job towards showing that their samples have very high ee's.Analysis of 30 crystals is an excellent attempt.If Nature Communications wants to be absolutely correct on this, I would suggest that "enantiomerically pure" be put in quotes and then somewhere in the manuscript the authors discuss that by analyses of 30 crystals the ee must be in the high 90's.Therefore, they are calling this high ee "enantiomercially pure." 2. The samples are prepared at low Si/Ge.This leads to low stability of the material.Note that the calcination was performed in dry air.Somewhere in the presentation, this limitation should be mentioned.It does not appear that this new organic structure directing agent provides for materials that can be synthesized at compositions significantly difference than previously published.
3. How were the compositions measured?There needs to be at least one sample that has chemical composition measured independently from the structural analyses.What is F content and what is the ion balance from a bulk elemental analysis?4.There is no such thing as a BET surface area for a material like this.There must be multilayered adsorption to use the BET correctly.A lot of people in this field misuse the BET equation.I suggest they remove BET surface area numbers as they are meaningless.It is appropriate to use pore volumes and they do have those listed already.5.It would have been nice to see some type of functional expression of the chirality.For example adsorption and/or catalysis.However, I believe that the structural work that has been accomplished is sufficient for publication in Nature Communications.
Overall, this is a nice piece of work.
Reviewer #2 (Remarks to the Author): The manuscript describes a very interesting chiral OSDA for the preparation of enantiomericallypure STW chiral zeolite, using a sugar-based cation derived from isomannide.The work is of great interest since it is the first clear demonstration of the crystallization of an enantiomerically-pure zeolite by using this particular chiral OSDAs.Although previous reports have shown at least enantio-enriched chiral zeolites with STW, CZP or ITV frameworks, this is the first clear proof of the enantiopurity of a chiral zeolite.A limitation, however, both in terms of characterization and application, is given by the fact that only one enantiomer of the zeolite, that imposed by the absolute configuration of the chiral sugar used as precursor, can be obtained (S-STW).Although the work is of high interest and correctly performed, with conclusions clearly supported by the data, however a number of issues need to be addressed: -The main question relates to the use of these new zeolites for asymmetric catalysis, as was done by Brand and coworkers in their original work about STW (ref. 20), where it was reported the asymmetric catalytic activity of STW chiral zeolites for the ring-opening of chiral linear epoxides with methanol or even larger alcohols (ref. 20 and ref. 2), as well as for the enantioselective adsorption of 2-butanol.Opposite chiral behaviors observed for both zeolite enantiomers clearly evidenced the asymmetric activity of the chiral zeolites.In this regard, have the authors tried their enantiopure chiral zeolite for asymmetric catalysis and adsorption of chiral substrates processes?The authors should comment on this on the manuscript, since this is a crucial issue.
-The authors analyze by computational methods the fit of the different cations (OSDA1 to 4) in the STW zeolite (Table S1 and Figure S3): with which STW polymorph (P6122 or P6322) were the calculations with the cations performed?In this regard, it would be highly interesting to study the interaction energies, in particular of OSDA3, in both STW crystalline polymorphs (P6122 and P6322) in order to see the distinct fit of each enantiomer of the organic cation in both crystalline zeolite polymorphs (similarly as was done by Brand et al. in ref. 20).Analysis of the different chiral host-guest match of both diastereomeric pairs would be very interesting to understand the transfer of the chirality of the ch-OSDA into the chiral zeolite growing; this information would add great value to the manuscript.
-The absolute configuration of the crystals of the STW zeolite are clearly determined by singlecrystal X-Ray Diffraction.Apart from the use of optical microscopy (Figure S9), have the authors considered the use of circular dichroism to characterize their samples?The material would not be active in the usual Electronic Circular Dichroism, but should be active in Vibrational Circular Dichroism, and if so, this could provide a fingerprint to characterize the handedness of STW chiral zeolites when single-crystal studies are not possible.
-The authors report that: "An important feature of isomannide is the absence of a specular analogue, rendering as a highly appropriate starting molecule for the synthesis of new enantiopure ch-OSDAs".However, as previously mentioned, this could represent a disadvantage since only one handedness of the zeolite, that imposed by nature, would be available for potential applications.-In the 13C NMR spectra (Figure S5) of the zeolite, bands corresponding to C4 and C5 split.What is the reason for such splitting?Is it because of a different environment of the corresponding C atoms (two Cs for each)?This might be related to the asymmetric position of the ch-OSDA within the zeolite, as determined from Rietveld, and this information would be interesting to understand the transfer of chirality into the zeolite.
-Si-STW has not been obtained with this OSDA, according to the authors.Have they tried to use seeds of silicogermanate-STW in order to favor the crystallization of Si-STW, or even to achieve smaller crystals more appropriate for applications?-Given the very limited number of references related to enantio-enriched chiral zeolites, some citations are missed: for instance, the first report of an enantiomerically-enriched zeolite by using nucleotides (derived from chiral sugars) (Zhang et al., Nucleotide-catalyzed conversion of racemic zeolite-type zincophosphate into enantioenriched crystals, Angew.Chem.Int. Ed. 2009, 48, 6049 -6051).On the other hand, more recent publications by de la Serna et al. have reached higher ee's than those mentioned in the current manuscript, of up to 55 % (de la Serna et al., Inversion of chirality in GTM-4 enantio-enriched zeolite driven by a minor change of the structure-directing agent, Chem.Commun.2022, 58, 13083; de la Serna et al., Asymmetric catalysis within chiral zeolitic nanospaces: Chiral host-guest match in GTM-3 zeolite, Catal. Today 2024, 426, 114389).
Reviewer #3 (Remarks to the Author): Sala et al report the synthesis of an enantiomorphically pure germanosilicate STW zeolite by using a sugar-derived chiral-organic structure-directing agent.The materials were characterized by powder and single-crystal x-ray diffraction, optical microscopy, scanning electron microscopy, NMR, and gas adsorption measurements.The evidence of the synthesis of an enantiomorphically pure STW zeolite was presented.The enantiomerically enriched STW germanosilicate zeolite has been reported previously.The novelty of this manuscript is to provide a new chiral-organic structuredirecting agent for synthesizing enantiomorphically pure STW zeolite, which merits its publication in Nat.Commun.However, the following comments need to be addressed before its acceptance for publication.1.In the Abstract and Conclusions, the authors stated that they used a "novel" or "innovative" zeolite synthesis approach to synthesize enantiomerically pure S-STW zeolite.The synthesis of chiral zeolite with a chiral OSDA is a known method.The statement is overstated.2. The application of the enantiomorphically pure STW zeolite in chiral separation or catalysis was not provided.This makes the work incomplete.3. CD spectra should be provided as additional evidence for enantiomorphically pure zeolite.4. The graphs in Figs 2 and 3 should be labeled and annotated.5. Fig. 2 and Fig. S9 clearly show that the STW samples are not pure, contaminated with amorphous materials.There are also small rod-like crystals in Fig S9 which are different with the STW crystals.What are they?These make the claim "The purity of the S-STW sample was confirmed by carrying out the Rietveld refinement" suspicious.In Fig. 4 there are also some peaks not due to the STW zeolite.Please explain.

Reviewer #1 (Remarks to the Author):
The work described in this manuscript is very good.The topic of chiral molecular sieves is appropriate for Nature Communica ons, and the results of sufficient significance to merit publica on.I have a few comment to hopefully assist in construc ng the final version of the manuscript.
1.There is really no way to prove that a powder is enan omerically pure.The authors have done a good job towards showing that their samples have very high ee's.Analysis of 30 crystals is an excellent a empt.If Nature Communica ons wants to be absolutely correct on this, I would suggest that "enan omerically pure" be put in quotes and then somewhere in the manuscript the authors discuss that by analyses of 30 crystals the ee must be in the high 90's.Therefore, they are calling this high ee "enan omercially pure." The referee is correct in no ng that it's challenging to determine absolute enan omeric purity.However, the use of standards labelled as 'enan omerically pure' as a reference point for 100% purity is widely spread in determining chirality's.We thank to the referee for apprecia ng our effort in analysing 30 crystals, which is a good start.This statement has been incorporated into the main manuscript in page 6, lines 15 to 18.However, to be 95% confident that our sample is over 95% enan omorphically pure, we would need to analyse at least 60 crystals.And if we want even higher purity or confidence levels, we would need to analyse hundreds of crystals, which is simply not feasible for most of the laboratories, including ours.
2. The samples are prepared at low Si/Ge.This leads to low stability of the material.Note that the calcina on was performed in dry air.Somewhere in the presenta on, this limita on should be men oned.It does not appear that this new organic structure direc ng agent provides for materials that can be synthesized at composi ons significantly difference than previously published.
The purpose of employing the sugar-based organic structure-direc ng agent (OSDA) for the synthesis of Ge-STW is not primarily enhancing the stability of the calcined zeolite.Rather, it serves as an effec ve method of transmi ng its chirality to the resul ng solid material.This novel OSDA does not alter the chemical composi on range of the inorganic framework of STW zeolites.Consequently, the referee's observa on regarding the instability of calcined Ge-STW upon exposure to atmospheric moisture is valid as it was stated in the previous manuscript (in the new version of the manuscript in page 4, lines 36 to 38.Nevertheless, we have also included this clarifica on in the updated manuscript in the figure cap on of Figure 4 of the main text.
3. How were the composi ons measured?There needs to be at least one sample that has chemical composi on measured independently from the structural analyses.What is F content and what is the ion balance from a bulk elemental analysis?
The samples Ge-STW described in this work were analysed by ICP (see table S2 that report the inorganic composi ons).The C, H, N and F contents were determined in some samples.The analy cal procedures were as follows: 50 mg of zeolite were dissolved in 1 mL of an acid solu on of 1:1:3 HF (40%): HNO3 (70%): HCl (33%), overnight.The resul ng solu on was diluted up to 50 mL using high pure water (MilliQ quality).The Si and Ge contents in the resul ng solu on were determined by ICP-OES on a ICP Varian 715-ES instrument.
C, H and N were determined on a EuroEA300 instrument from Eurovector.
The Fluoride contents of some samples were determined by measuring their 19F-MAS-NMR spectra of the weighted STW samples.The intensi es of the observed resonances were integrated and compared to a Fluoride standard (in this case, F-containing zeolite BEC).The Fluoride contents were in all cases between 1.8 to 1.9 wt%, in good agreement to that obtained from single-crystal diffrac on data (i.e.6F/U.C).
These paragraphs have been included in the experimental sec on in page 15, lines 7 to 14 of the main manuscript.
4. There is no such thing as a BET surface area for a material like this.There must be mul -layered adsorp on to use the BET correctly.A lot of people in this field misuse the BET equa on.I suggest they remove BET surface area numbers as they are meaningless.It is appropriate to use pore volumes and they do have those listed already.The referee's concern regarding the BET-area values is acknowledged.However, it's important to note that these values are widely u lized in scien fic literature.Addi onally, the Interna onal Union of Pure and Applied Chemistry (IUPAC) recognizes their use as an apparent surface area, considering them as a valuable adsorbent "fingerprint" (new reference 40 in the manuscript).To address this, we have amended the terminology from 'BET area' or 'BET surface area' to 'apparent BET surface area', with the relevant reference being duly incorporated in page 15, line 24 of the main manuscript and in the table S3 in Supplementary materials.5.It would have been nice to see some type of func onal expression of the chirality.For example adsorp on and/or catalysis.However, I believe that the structural work that has been accomplished is sufficient for publica on in Nature Communica ons.Overall, this is a nice piece of work.
Thank you very much for your comment.We a empted adsorp on experiments with S-2butanol and R-2-butanol on the 2-STW sample, following the findings from Davis et al., who reported preferen al adsorp on of S-2-butanol on enriched S-STW zeolite (and vice versa for R-2-butanol).However, we did not observe any vapor uptake on our sample.To verify the reten on of microporosity, we measured the CO2 adsorp on isotherm before and a er the alcohol adsorp on experiments, being both iden cal and therefore, confirming that there is no loss of microporosity during the adsorp on experiments.The lack of alcohol adsorp on may be a ributed to the large crystal size of our zeolite, necessary for single crystal structural elucida on, but hindering diffusion through the helicoidal channel of the STW sample.
Addi onally, cataly c experiments were performed to inves gate epoxide ring-opening reac ons u lizing aluminum-containing STW samples (named as Al-S-STW) as catalysts.Unfortunately, the results of these experiments demonstrated notably low epoxide conversion rates across various chain lengths, as outlined in the table below (provided solely for referee evalua on purposes).This table shows that the achieved conversion for 1,2-epoxyhexane ring-opening was 2%, with an approximate 1:2 ra o of product A to product B., with an enan omeric excess ranging between 4 to 3.5% in the resultant products.When evalua ng shorter alkyl chain epoxides, such as 1,2-epoxybutane, a higher conversion rate of 6% was achieved, albeit with enan omeric excesses in the products ranging from 1.5 to 2.5%.

Material epoxide Conversion (%) Selec vity to A (%) Selec vity to B (%)
When compared with the results obtained using another zeolite with a larger pore size, we observed a significant increase in conversion, reaching nearly quan ta ve values.This supports our hypothesis that poor diffusion of reactants through the smaller pores of the material limits reac on efficiency.
This limita on in ac vity and selec vity can be a ributed to the very large crystal size of the catalysts, hampering the diffusion of reactants and/or products through the helicoidal pores during the reac on, and therefore the limited ac vity is mostly occurring at the external surface of the crystals of zeolite STW.
Despite efforts to reduce the crystal size of the S-STW materials to avoid these limita ons, we did not observe a significant decrease in crystal size for well-crystallized solids.These limita ons have been acknowledged in page 8, lines 19 to 30 of the revised version of the manuscript.

Reviewer #2 (Remarks to the Author):
The manuscript describes a very interes ng chiral OSDA for the prepara on of enan omericallypure STW chiral zeolite, using a sugar-based ca on derived from isomannide.The work is of great interest since it is the first clear demonstra on of the crystalliza on of an enan omerically-pure zeolite by using this par cular chiral OSDAs.Although previous reports have shown at least enan o-enriched chiral zeolites with STW, CZP or ITV frameworks, this is the first clear proof of the enan opurity of a chiral zeolite.
A limita on, however, both in terms of characteriza on and applica on, is given by the fact that only one enan omer of the zeolite, that imposed by the absolute configura on of the chiral sugar used as precursor, can be obtained (S-STW).Although the work is of high interest and correctly performed, with conclusions clearly supported by the data, however a number of issues need to be addressed: -The main ques on relates to the use of these new zeolites for asymmetric catalysis, as was done by Brand and coworkers in their original work about STW (ref. 20), where it was reported the asymmetric cataly c ac vity of STW chiral zeolites for the ring-opening of chiral linear epoxides with methanol or even larger alcohols (ref. 20 and ref. 2), as well as for the enan oselec ve adsorp on of 2-butanol.Opposite chiral behaviors observed for both zeolite enan omers clearly evidenced the asymmetric ac vity of the chiral zeolites.In this regard, have the authors tried their enan opure chiral zeolite for asymmetric catalysis and adsorp on of chiral substrates processes?The authors should comment on this on the manuscript, since this is a crucial issue.
Thank you very much for your comment.We a empted adsorp on experiments with S-2butanol and R-2-butanol on the 2-STW sample, following the findings from Davis et al., who reported preferen al adsorp on of S-2-butanol on enriched S-STW zeolite (and vice versa for R-2-butanol).However, we did not observe any vapor uptake on our sample.To verify the reten on of microporosity, we measured the CO2 adsorp on isotherm before and a er the alcohol adsorp on experiments, being both iden cal and therefore, confirming that there is no loss of microporosity during the adsorp on experiments.The lack of alcohol adsorp on may be a ributed to the large crystal size of our zeolite, necessary for single crystal structural elucida on, but hindering diffusion through the helicoidal channel of the STW sample.
Addi onally, cataly c experiments were performed to inves gate epoxide ring-opening reac ons u lizing aluminum-containing STW samples (named as Al-S-STW) as catalysts.
Unfortunately, the results of these experiments demonstrated notably low epoxide conversion rates across various chain lengths, as outlined in the table below (provided solely for referee evalua on purposes).This table shows that the achieved conversion for 1,2-epoxyhexane ring-opening was 2%, with an approximate 1:2 ra o of product A to product B., with an enan omeric excess ranging between 4 to 3.5% in the resultant products.When evalua ng shorter alkyl chain epoxides, such as 1,2-epoxybutane, a higher conversion rate of 6% was achieved, albeit with enan omeric excesses in the products ranging from 1.5 to 2.5%.

Material epoxide Conversion (%) Selec vity to A (%) Selec vity to B (%)
When compared with the results obtained using another zeolite with a larger pore size, we observed a significant increase in conversion, reaching nearly quan ta ve values.This supports our hypothesis that poor diffusion of reactants through the smaller pores of the material limits reac on efficiency.This limita on in ac vity and selec vity can be a ributed to the very large crystal size of the catalysts, hampering the diffusion of reactants and/or products through the helicoidal pores during the reac on, and therefore the limited ac vity is mostly occurring at the external surface of the crystals of zeolite STW.
Despite efforts to reduce the crystal size of the S-STW materials to avoid these limita ons, we did not observe a significant decrease in crystal size for well-crystallized solids.These limita ons have been acknowledged in page 8, lines 19 to 30 of the revised version of the manuscript.
-The authors analyze by computa onal methods the fit of the different ca ons (OSDA1 to 4) in the STW zeolite (Table S1 and Figure S3): with which STW polymorph (P6122 or P6322) were the calcula ons with the ca ons performed?In this regard, it would be highly interes ng to study the interac on energies, in par cular of OSDA3, in both STW crystalline polymorphs (P6122 and P6322) in order to see the dis nct fit of each enan omer of the organic ca on in both crystalline zeolite polymorphs (similarly as was done by Brand et al. in ref. 20).Analysis of the different chiral host-guest match of both diastereomeric pairs would be very interes ng to understand the transfer of the chirality of the ch-OSDA into the chiral zeolite growing; this informa on would add great value to the manuscript.
We appreciate the reviewer's insigh ul comment, and indeed, we didn't specify in the manuscript that all our calcula ons were conducted in the S enan omorph of STW, corresponding to the pure enan omorph we synthesized.Consequently, this aspect has been duly incorporated into the updated version as follows: Main manuscript: Page 4, line 6 and 7: "only OSDA3 is stabilized in the micropore of this zeolite" has been changed by "only OSDA3 is stabilized in the micropore of S-STW (P6 1 22 space group)".
Cap on of Figure S3: "in STW zeolite" has been changed by "in S-STW zeolite (P6 1 22 space group)" Cap on of Table S1: "Calculated STW-OSDA" has been changed by "Calculated S-STW-OSDA" We would like to stress here that the two enan omorphs do not belong to the space groups indicated above by the reviewer but rather P6 1 22 and P6 5 22, as indicated in the main manuscript: "In this case, six crystals were indexed in the space group P6 5 22 (enan omorph R) and five in the space group P6 1 22 (enan omorph S) indica ng that a racemic mixture of both enan omorphs was formed." More importantly, in response to the reviewer's sugges on, we have op mized the loca on of OSDA3 in R-STW.The results are shown in the new Figure S4 along with corresponding explanatory text in page 4, lines 11 to 13, which evidence that the curvature of OSDA3 does not align well with the helicoidal channel of R-STW.Specifically, our Monte Carlo algorithm required 10 mes more cycles (120000) to determine this geometry and could only accommodate one OSDA3 molecule, whereas in the case of S-STW, three OSDA3 molecules could be readily allocated within its micropore system using the same Monte Carlo algorithm.
-The absolute configura on of the crystals of the STW zeolite are clearly determined by singlecrystal X-Ray Diffrac on.Apart from the use of op cal microscopy (Figure S9) have the authors considered the use of circular dichroism to characterize their samples?The material would not be ac ve in the usual Electronic Circular Dichroism, but should be ac ve in Vibra onal Circular Dichroism, and if so, this could provide a fingerprint to characterize the handedness of STW chiral zeolites when single-crystal studies are not possible.
We conducted circular dichroism measurements in the UV-visible region.However, the results obtained were inconclusive as dichroic signals were observed at certain angles of incidence, while they were absent at others.For the purpose of review, we have included examples of spectra collected from one of our samples at different angles.In the figure below, a clear dichroic signal at 200 nm is evident at 0 and 180º, while no signal is observed at 90º.This observa on may suggest the presence of chirality in the studied solids, although conclusive interpreta on needs further inves ga on, which falls outside our current exper se.
Addi onally, we a empted to follow the referee's recommenda on of measuring the vibra onal circular dichroism of the reported STW materials.This spectroscopic technique is unconven onal, and unfortunately, we were unable to locate any physical-chemical service at Spanish universi es or Public Research Ins tutes offering this capability.
Instead, we have relied on single-crystal X-ray diffrac on (SCXRD) and the Flack parameter as our primary methodologies.These are widely accepted in the scien fic community for determining the chirality of crystal structures.These methods provide a more direct and unambiguous way to assess the enan omorphic purity of the zeolites we have synthesized, ensuring that our conclusions are robust.
-The authors report that: "An important feature of isomannide is the absence of a specular analogue, rendering as a highly appropriate star ng molecule for the synthesis of new enan opure ch-OSDAs".However, as previously men oned, this could represent a disadvantage since only one handedness of the zeolite, that imposed by nature, would be available for poten al applica ons.The referee's comment is correct, as our synthesis route indeed only yields one enan omorph of the STW zeolite.However, in nature, chiral compounds typically appear in either the R or S configura on, maintaining a high level of purity.Achieving such enan omeric excess through synthe c routes is challenging, o en resul ng in impuri es of the opposite enan omer during organic synthesis.Therefore, our approach in this study was to u lize natural chiral products that lack a counterpart chiral enan omer.This enables the synthesis of pure chiral organic structuredirec ng agents (OSDAs), as racemiza on is not possible.Furthermore, the syntheses described in this work are very simple, facilita ng the prepara on of OSDAs at a mul gram scale necessary for studies on new zeolite synthesis.
-In the 13C NMR spectra (Figure S5) of the zeolite, bands corresponding to C4 and C5 split.What is the reason for such spli ng?Is it because of a different environment of the corresponding C atoms (two Cs for each)?This might be related to the asymmetric posi on of the ch-OSDA within the zeolite, as determined from Rietveld, and this informa on would be interes ng to understand the transfer of chirality into the zeolite.
The presence of four dis nct configura ons of the encapsulated OSDA within pore system of the S-STW zeolite could account for the spli ng observed in the 13C-CP-SS-NMR spectrum of the as-synthesized material.The different docking of the organic molecules within the helicoidal channel induces slight modifica ons in the surrounding environment of the carbon nuclei of the OSDA, leading to the observed signal spli ng in the 13C-NMR spectrum.The explanatory text has been included in the figure cap on of Figure S5 of the new manuscript.
-Si-STW has not been obtained with this OSDA, according to the authors.Have they tried to use seeds of silicogermanate-STW in order to favor the crystalliza on of Si-STW, or even to achieve smaller crystals more appropriate for applica ons?
The use of STW seeds to increase the Si/Ge ra o and/or reduce crystal size has been inves gated, albeit with limited success.Seeding with a high concentra on of Ge-containing STW zeolite (up to 30% seeding) has led to the forma on of amorphous solids when a emp ng to increase the Si/Ge ra o.In addi on, a empts to diminish crystal size by introducing seeds into the synthesis gel were unsuccessful, resul ng in the forma on of Ge-containing STW zeolites with crystal sizes similar to those of unseeded samples or in the forma on of impuri es in the final solid.A statement addressing these outcomes has been incorporated accordingly in page 8, lines 19 to 30.
-Given the very limited number of references related to enan o-enriched chiral zeolites, some cita ons are missed: for instance, the first report of an enan omerically-enriched zeolite by using nucleo des (derived from chiral sugars) (Zhang et al., Nucleo de-catalyzed conversion of racemic zeolite-type zincophosphate into enan oenriched crystals, Angew.Chem.Int. Ed. 2009, 48, 6049 -6051).On the other hand, more recent publica ons by de la Serna et al. have reached higher ee's than those men oned in the current manuscript, of up to 55 % (de la Serna et al., Inversion of chirality in GTM-4 enan o-enriched zeolite driven by a minor change of the structure-direc ng agent, Chem.Commun.2022, 58, 13083; de la Serna et al., Asymmetric catalysis within chiral zeoli c nanospaces: Chiral host-guest match in GTM-3 zeolite, Catal.Today 2024, 426, 114389).
We are grateful to the reviewer for this comment.The missing references have been added to the updated version of the manuscript as new references 11, 21, 25 and 26.All the references have been renumbered.

Reviewer #3 (Remarks to the Author):
Sala et al report the synthesis of an enan omorphically pure germanosilicate STW zeolite by using a sugar-derived chiral-organic structure-direc ng agent.The materials were characterized by powder and single-crystal x-ray diffrac on, op cal microscopy, scanning electron microscopy, NMR, and gas adsorp on measurements.The evidence of the synthesis of an enan omorphically pure STW zeolite was presented.The enan omerically enriched STW germanosilicate zeolite has been reported previously.The novelty of this manuscript is to provide a new chiral-organic structure-direc ng agent for synthesizing enan omorphically pure STW zeolite, which merits its publica on in Nat.Commun.However, the following comments need to be addressed before its acceptance for publica on.
1.In the Abstract and Conclusions, the authors stated that they used a "novel" or "innova ve" zeolite synthesis approach to synthesize enan omerically pure S-STW zeolite.The synthesis of chiral zeolite with a chiral OSDA is a known method.The statement is overstated.The reviewer's comment is right, as chiral organic structure-direc ng agents (OSDAs) have been u lized previously a emp ng to produce chiral zeolites, albeit with varying degrees of success.Many previous efforts have resulted in non-chiral zeolites, as we also report in this study, while a few have achieved significant enrichments in R and S enan omorphic zeolites.However, none have been able to claim the synthesis of a 'pure enan omorph' as we demonstrate in this work.
The terms 'novel' and 'innova ve' in our study specifically refer to the u liza on of sugars as chiral building blocks, as emphasized in the tle, to synthesize unique chiral organic structuredirec ng agents (OSDAs).These newly developed chiral compounds exhibited remarkable selec vity in impar ng their chirality to the zeolite.To our knowledge, the approach of employing sugar-derived OSDAs has not been previously explored in the open literature or patented methods.Furthermore, this innova ve strategy has led to the synthesis of enan omorphically pure zeolite, thereby enhancing its novelty.We firmly believe that these aspects jus fy characterizing our work as 'novel' and/or 'innova ve'.This discovery may pave the way for a new research direc on in the synthesis of chiral porous solids.
2. The applica on of the enan omorphically pure STW zeolite in chiral separa on or catalysis was not provided.This makes the work incomplete.
Thank you very much for your comment.We a empted adsorp on experiments with S-2butanol and R-2-butanol on the 2-STW sample, following the findings from Davis et al., who reported preferen al adsorp on of S-2-butanol on enriched S-STW zeolite (and vice versa for R-2-butanol).However, we did not observe any vapor uptake on our sample.To verify the reten on of microporosity, we measured the CO2 adsorp on isotherm before and a er the alcohol adsorp on experiments, being both iden cal and therefore, confirming that there is no loss of microporosity during the adsorp on experiments.The lack of alcohol adsorp on may be a ributed to the large crystal size of our zeolite, necessary for single crystal structural elucida on, but hindering diffusion through the helicoidal channel of the STW sample.
Addi onally, cataly c experiments were performed to inves gate epoxide ring-opening reac ons u lizing aluminum-containing STW samples (named as Al-S-STW) as catalysts.Unfortunately, the results of these experiments demonstrated notably low epoxide conversion rates across various chain lengths, as outlined in the table below (provided solely for referee evalua on purposes).This table shows that the achieved conversion for 1,2-epoxyhexane ring-opening was 2%, with an approximate 1:2 ra o of product A to product B., with an enan omeric excess ranging between 4 to 3.5% in the resultant products.When evalua ng shorter alkyl chain epoxides, such as 1,2-epoxybutane, a higher conversion rate of 6% was achieved, albeit with enan omeric excesses in the products ranging from 1.5 to 2.5%.

Material
When compared with the results obtained using another zeolite with a larger pore size, we observed a significant increase in conversion, reaching nearly quan ta ve values.This supports our hypothesis that poor diffusion of reactants through the smaller pores of the material limits reac on efficiency.
This limita on in ac vity and selec vity can be a ributed to the very large crystal size of the catalysts, hampering the diffusion of reactants and/or products through the helicoidal pores during the reac on, and therefore the limited ac vity is mostly occurring at the external surface of the crystals of zeolite STW.
Despite efforts to reduce the crystal size of the S-STW materials to avoid these limita ons, we did not observe a significant decrease in crystal size for well-crystallized solids.These limita ons have been acknowledged in page 8, lines 19 to 30 of the revised version of the manuscript.
3. CD spectra should be provided as addi onal evidence for enan omorphically pure zeolite.
We conducted circular dichroism measurements in the UV-visible region.However, the results obtained were inconclusive as dichroic signals were observed at certain angles of incidence, while they were absent at others.For the purpose of review, we have included examples of spectra collected from one of our samples at different angles.In the figure below, a clear dichroic signal at 200 nm is evident at 0 and 180º, while no signal is observed at 90º.This observa on may suggest the presence of chirality in the studied solids, although conclusive interpreta on needs further inves ga on, which falls outside our current exper se.
Addi onally, we a empted to measure the vibra onal circular dichroism of the reported STW materials.This spectroscopic technique is unconven onal, and unfortunately, we were unable to locate any physical-chemical service at Spanish universi es or Public Research Ins tutes offering this capability.
Instead, we have relied on single-crystal X-ray diffrac on (SCXRD) and the Flack parameter as our primary methodologies.These are widely accepted in the scien fic community for determining the chirality of crystal structures.These methods provide a more direct and unambiguous way to assess the enan omorphic purity of the zeolites we have synthesized, ensuring that our conclusions are robust and scien fically sound.
4. The graphs in Figs 2 and 3 should be labeled and annotated.
Thanks to the reviewer for this comment.The figures 2 and 3 have been modified according to the referee's indica ons.SEM images in Figure 2 show several prepara ons of S-STW-2.The top-le image demonstrates the homogeneity in crystal size, while the remaining images provide a closer view of the crystals, revealing minor impuri es due to sample prepara on.The presence of breakage in S-STW crystals, as shown in the bo om right image, may account for other observed 'impuri es' in the bo om-le images.Addi onally, residues of carbon ribbon are observed in the top-right image, as the samples were mounted on double-sided adhesive carbon tape for SEM measurements.
The referee's observa on regarding the rod-like crystals in Figure S10 (in previous manuscript, Fig. S9) is correct.We collected one of these rod-like crystals and obtained its single crystal X-ray diffrac on data, revealing a unit cell consistent with quartz-like GeO2.However, it's important to note that this impurity appeared only in this par cular prepara on and was not evident in all the other syntheses of S-STW-2 reported in this work.The number of rod-like crystals is significantly lower than those exhibi ng the characteris c hexagonal bipyramid shape of STW, and their crystal size is several orders of magnitude smaller.Therefore, the content of this impurity is negligible for most common characteriza on techniques.
Rietveld refinements further support the very high purity of the materials obtained from gels with a Si/Ge ra o of 2. Figure 4 displays the experimental X-ray pa ern and calculated profile, along with the corresponding difference.The residuals of the fi ng are minimal, indica ng the absence of any detectable phase other than S-STW.
Regarding the weak and broad diffrac on peak observed between 6.5 and 7 degrees in Figure 4, this peak is a ributed to the high-temperature chamber XRK900 used for the 'in-situ' calcina on of the S-STW-2 material.This 'fake' diffrac on is also evident in several of our previous publica ons where the same a achment was u lized (see for instance Fig S7 and S9 in Chemical Communica ons 2012, 48, 215-217 and Fig S12 in Science, 2017, 358, 1068-1071 among others).Thus, the 'fake' peak can be safely treated as part of the background.
In conclusion, we emphasise that the S-STW-2 samples prepared in this work exhibit very high purity and crystallinity.
.e.: 0) 54 (e.e.: 0) Reac on temperature: 25ºC, 7 mmol epoxide, 14 mmol i-propanol, 30 mg A-S-STW, reac on me: 1h Product A Product B on temperature: 25ºC, 7 mmol epoxide, 14 mmol i-propanol, 30 mg A-S-STW, reac on me: 1h Product A Product B 5. Fig.2and Fig.S9clearly show that the STW samples are not pure, contaminated with amorphous materials.There are also small rod-like crystals in Fig S9 which are different with the STW crystals.What are they?These make the claim "The purity of the S-STW sample was confirmed by carrying out the Rietveld refinement" suspicious.In Fig.4there are also some peaks not due to the STW zeolite.Please explain.